Earlier this month, the World Health Organization (WHO) reported some troubling news. On September 20, a man from Kween District in eastern Uganda was admitted to a local hospital after developing fever, bleeding, vomiting and diarrhea. According to WHO, the man, a 35-year-old herdsman, frequently hunted near an area known to host bat-inhabited caves. He died five days later, after being transferred to a nearby hospital, but no blood samples were collected at that time and his death was not attributed to a specific disease.

Some three weeks later, his sister, who had cared for him and helped with burial rituals, was hospitalized with similar symptoms and died shortly after. Posthumous samples confirmed the presence of Marburg virus, a microbe that can infect both animals and humans. Shortly afterward, the Ugandan Ministry of Health declared an outbreak of Marburg virus disease (MVD) in Kween District.

But the story didn’t end here. A brother of these two also was diagnosed with MVD — but before he died, the man travelled to Kenya, potentially spreading the virus. Ugandan and Kenyan health authorities, WHO, UNICEF, and the Kenya Red Cross Society are watching for evidence of further dissemination of this virus.

The outbreak, which may have begun when the first man was infected by a bat carrying the virus, is an example of a disease outbreak of zoonotic origin — one that can be transmitted from animals into humans. It appears that this incident has been limited to a local spillover of an animal-borne virus into humans. But the international travel component is a very real reminder that such a course of events can lead to a zoonotic pandemic, a worldwide spread of a pathogen — most often a virus — transmitted from animals to humans. From severe acute respiratory syndrome (SARS) to AIDS and Ebola, zoonotic diseases cause more than a billion cases of illness each year. As humans increasingly encroach on wildlife territory and increasingly travel long distances in short times, the threat of zoonotic pandemics is growing. At the same time, so are efforts to prevent or curtail them.

Recipe for a Pandemic

Viruses have been moving between organisms for millions of years. And not always in a way that causes harm: Animals and humans alike host millions of different microorganisms, many of which are beneficial.

“We live in an essentially microbial world, and we are actually complex ecosystems comprising a whole lot of microorganisms,” says Fabian Leendertz, head of the Epidemiology of Highly Pathogenic Microorganisms group at the Robert Koch Institute in Berlin. “Some are pathogenic, but most of them live at peace with us.”

For those that do harm humans, the first step is to come in contact with us. And that’s becoming more and more likely as we invade pristine forests in search of food, building materials, space for commercial developments or land upon which we can create new grassland for our livestock — or catch critters for bushmeat, pets or the “wildlife selfie” trade.

“The typical formula for a zoonotic outbreak starts with a human getting into contact to a viral host, like a bat or rodent. Then just a dash of luck that specific host carries [a] virus capable of jumping species barriers, and the epidemic starts from here,” Leendertz says.

Bushmeat is one channel through which viruses can travel from wild animals to humans. Photo courtesy of Karsing Megu & Victor Meyer-Rochow.

Sometimes a zoonotic virus can jump directly into humans, as occurred with the Marburg virus. Other viruses, like the virus responsible for SARS, first spill over from a wildlife species into a domestic animal host, where the virus multiplies and evolves to become better able to infect a human host.

Once a zoonotic virus infects a human, different things can happen. If it is extremely virulent, it will rapidly kill its human host — which from a strictly epidemiological perspective can be seen as beneficial, because there may be fewer chances that the virus will spread to others. But if the virus takes some time before it makes the person sick and is easily transmitted from one person to another, a larger problem could occur.

“All you need then is for host to interact with more people, to move around and pass along the virus,” says Leendertz. “Before we even know about the virus, we can end up with a full-blown epidemic on our hands. This was the case with the HIV epidemic.”

Detection and Discovery

What can be done to reduce the likelihood that new zoonotic viruses will emerge? And how can we become better prepared to deal with those that do?

The PREDICT project, led by the One Health Institute at the School of Veterinary Medicine at the University of California, Davis, has been working since 2009 to identify viruses in wildlife such as bats, rodents and nonhuman primates around the world. The goal is to find viruses with potential for zoonotic outbreaks before they become a pandemic. The hope is that learning about these viruses will help governments design policies that can better deal with outbreaks.

The project is a worldwide collaboration, including scientists, government personnel, physicians, veterinarians, biologists, laboratory technicians, students and members of the general public from across 35 countries in Asia and Africa.

PREDICT researchers have identified hundreds of known (blue) and previously unknown (red) viruses with zoonotic potential in samples from humans and wildlife around the world. The size of each circle indicates the relative number of viruses found. Image courtesy of PREDICT

In the first phase of the PREDICT project, completed in 2014, researchers collected blood and tissue samples from wildlife and humans from across the world. These samples were tested for the presence of viruses with the goal of understanding where and how viruses spread from other animals into humans.

According to Tracey Goldstein, co-lead for PREDICT’s viral detection and discovery team based at UC Davis, as of October 2017 PREDICT had detected 1,044 distinct viruses present in wildlife and humans, of which 864 were newly discovered. It’s hard to say which of these new viruses can cause us harm, but the PREDICT team has compared their DNA sequences with those of known pathogenic viruses in order to identify potentially dangerous viruses. “About 5 percent of the new viruses have been prioritized​ so far for further study to understand their potential of causing disease in humans. The number of viruses we would like to understand better are likely to increase as we detect more of them,” Goldstein says.

But what matters most is not how many viruses were found, but where. “We have detected some of these viruses in more than one country or in more than one host species,” Goldstein says. This information ought to help PREDICT identify what countries should be considered high risk for viral spillover from animals to humans. This information may help policy-makers and others develop improved and more targeted surveillance, detection and prevention guidelines to address specific threats.

By comparing the DNA sequences of known pathogenic viruses with those discovered by PREDICT, researchers found that potentially harmful viruses are widespread across the globe. In Malaysia, for example, they found a new enterovirus species in a Bornean orangutan. Also found harbouring enteroviruses were five chimpanzees in the Democratic Republic of Congo and two mice in Cameroon. Enteroviruses are known to cause a wide range of symptoms in humans, from mild respiratory conditions to disorders of the central nervous system.

Coronaviruses related to the viruses responsible for SARS and Middle East respiratory syndrome (MERS) were found in Malaysia, Bolivia, China and Uganda, mostly in bats. One SARS-like coronavirus found in China called HKU3, was particularly troubling, PREDICT researchers say, because it shares many similarities with the human SARS coronavirus.

Several new members of the Rhabdoviridae familywere found in Thailand, Indonesia, Tanzania and Republic of Congo, mostly in bat hosts. Some members of this family cause rabies or other types of fatal encephalitis in humans and other animals.

PREDICT has now moved into a second phase, PREDICT-2, with the scope broadened to include collecting samples from livestock as well as humans and wildlife. This new approach will serve to reveal viruses that already made the jump and are being shared by humans and other animals.

“This is the next step to better understand how viruses move between animals and people, as once you identify the viruses that have made the jump from wildlife into humans we can begin to understand what allowed this to happen and if they could be pathogenic,” Goldstein says.

PREDICT not only has identified viruses, it also has built infrastructure in many countries that allows for the detection and surveillance of zoonotic outbreaks. In these countries PREDICT has established protocols and trained personnel to identify viruses and handle animal samples safely. According to PREDICT, more than 3,500 individuals have been trained in the basic skills needed to respond to a zoonotic disease outbreaks in more than 35 countries across Latin America, Africa and Asia since 2009.

“Along with a more prepared workforce, many of these countries now have improved infrastructure and knowledge in place that allow for early detection of potentially zoonotic events that can enable more rapid response to new outbreaks,” says David John Wolking, global operations officer for the One Health Institute and member of the PREDICT team.

Global Virome Project

Another project that is currently in its initial phase is the Global Virome Project (GVP), first proposed in 2016 by a group of international stakeholders that included researchers, policy-makers and representatives from the public and private sector. This project seeks to detect and sequence the DNA of almost all viruses found in wildlife with potential to cause a human pandemic. Having a better understanding of the DNA makeup of viruses present in animals may help future studies identify viruses that are more likely to make the jump into humans.

Researchers involved with the development of the GVP are aiming to identify about half a million viruses, and estimate that it will cost around US$3.4 billion over the next 10 years to complete their goals. The results of this ambitious project could serve as a valuable reference database for future studies focused on identifying the main drivers and other factors to better understand how zoonotic outbreaks may occur.

While the price tag may seem hefty, it is a fraction of the costs associated with responding to past zoonotic outbreaks, such as SARS (more than US$50 billion) or influenza (US$570 billion per year). And that’s just the beginning of the benefits, says GVP group leader Linfa Wang, director of the emerging infectious diseases program at Duke-NUS Medical School, a collaboration between Duke University and the National University of Singapore.

“In addition, the ambitious aim of GVP to create the atlas of viruses in the world will benefit not only those interested in emerging zoonotic diseases, but also the general scientific community in general, as it will also teach us new lessons in evolutionary biology, environmental impact, farming practice, urban development” and more, Wang says.

Policy and Capacity

But what happens once we know about all the viruses we share with wildlife? Scientists hope the results from PREDICT will serve as the basis for future projects, studies, and policies. For example, policy-makers can use PREDICT information to make decisions about how and where to invest health-care resources. Likewise, wide-reaching institutions like the U.S. Centers for Disease Control and Prevention (CDC) can benefit from this information, because it might provide guidance on identifying countries representing a high risk of zoonotic outbreak.

Today, the CDC and USAID, through the Global Health Security Agenda launched in February 2014, are helping governments, international organizations, and non-governmental stakeholders build their technical capacity to respond to infectious diseases in over 50 countries.

The details on the whereabouts of novel viruses is a crucial component of this complex team effort. Thanks to these efforts, countries like Uganda, Vietnam and Ethiopia now have a network of laboratories with diagnostic capabilities and personnel trained in optimal emergency responses to disease outbreaks.

These capabilities have already been shown to be beneficial: They helped contain the recent Marburg outbreak in Uganda.